Adolescents low in socioeconomic status (SES) are nearly twice as likely to smoke cigarettes or vape and are more likely to use alcohol, cannabis, and illicit drugs than high-SES adolescents. This study will add to our understanding of adolescent substance use because it will examine SES discrimination. SES discrimination refers to the bias that individuals experience based on SES. Minority stress theory highlights how the stress experienced from discrimination is associated with substance use. Indeed, adult studies show that SES discrimination is positively associated with substance use. Yet, this line of inquiry has not been extended to adolescents. To our knowledge, there is only one study, and it indicated that maternal SES discrimination was positively associated with adolescent tobacco use. Recognizing a gap in the field, the PI created a new conceptual model for adolescent SES discrimination that includes overt (harassment) and subtle (microaggressions) forms. The model draws from adult studies on SES, racial/ethnic, and sexual orientation discrimination and adolescent studies on racial/ethnic and gender discrimination. The PI’s new preliminary work supports the model and shows how overt SES discrimination is positively associated with tobacco use, even after controlling for SES. The proposed research will advance our knowledge with three specific aims: To (1) examine how adolescents’ experiences with SES discrimination intersect with discrimination based on race/ethnicity, gender, and sexual orientation, (2) determine how SES discrimination is associated with substance use in adolescents, controlling for discrimination based on race/ethnicity, gender, and sexual orientation, and (3) investigate how associations between SES discrimination and substance use are moderated by subgroups, including SES, race/ethnicity, gender, and sexual orientation. Providing new knowledge is critical for informing programs that reduce and prevent substance use by targeting SES discrimination. We propose a mixed-methods study that includes interviews (N = 40) and surveys (N = 800) in 2 public high schools. The schools have a broad representation of SES (School 1 includes 77% low-income students and School 2 includes 20% low-income students). The study will be conducted in an experienced university lab that has established long-term partnerships with the high schools. Active consent procedures will be used. Consistent with the R16 aims, underrepresented students will be extensively involved. The PI’s track record with mentoring includes 50 undergraduate and 20 graduate students, 4 students advanced to PhDs, and 28 publications with student co-authors. Strategies to recruit and train students are planned.